Cell-cell adhesion between isotype and heterotype cells, and molecule-cell interactions, will be studied with viable or functioning cells. Monitoring of cell association reactions will utilize measurement of heats produced. Initial association phenomena, and later time dependent processes as segregation proceeds, will be studied. The consequences of varying techniques used for preparation of separated cells from tissue will be evaluated. Assay methods will be developed for monitoring cells which have been subjected to physical stress (temperature variation), and biochemical stress such as limited extraction of endogenous compounds or contact with foreign surfaces. Attempts to reverse effects of stress will be made by returning extracted compounds, and by introducing drugs. Modified cells will be titrated by foreign cells which adhere to them. The number of apparent interaction sites, 'stoichiometry', will be evaluated. Besides tissue cells, certain tumor cells, and platelets and erythrocytes will be used. Heats of specific cell functions, cell requirements, and cell behavior will be monitored. Examples are neutrophil phagocytosis and platelet adhesion, nutrient requirements, response to agglutinating and chemotactic agents, and to certain drugs. In collaborative work, perfusion calorimetry (a new design) will be used to resolve sequential events in embryonic development of tumor nuclear transplant frog eggs. The instruments to be constructed have three principal features: (1) Small sample sizes; needle biopsy amounts of cells, and nanocalorie range capability (2) Rapid settling into base lines (3) Reaction vessel interiors which are biologically benign. A new thermopile construction will be carried out via recent electronics fabrication technology.